How does the brain control hunger, and how does this instinctual motivational drive compel us to eat? Everyone experiences hunger, and some do battle with it, on a daily basis. Importantly, abnormalities of this drive (too much or too little) causes serious disorders ranging from obesity to anorexia nervosa.

Efforts to elucidate the biological basis for hunger and the means by which hunger compels us to eat, have unfortunately been stymied by the complexity of brain interconnections. With recently developed approaches for studying neural circuits in a highly selective manner, this complexity can now be “solved”. Using these approaches, we are uncovering the “wiring diagram” that underlies brain control of hunger, and the means by which hunger compels us to eat.

Using a variety of genetic engineering approaches, including CRISPR/Cas9, we are creating many lines of mice that express Cre recombinase, as well as other recombinases, in many different, very select subsets of neurons – especially in neurons located in brain regions controlling hunger. These mice are then used by us, as well as by scientists around the world, to express a multitude of “tools” specifically in the Cre-expressing subsets of neurons. With such “tools” expressed in each specific subset of neurons, it is then possible to:  a) map connections of the Cre-expressing neurons to determine the “upstream” neurons that talk to them, and the “downstream” neurons that they talk to (upsteam neurons à Cre-expressing neurons à downstream neurons), b) experimentally manipulate the activity of the Cre-expressing neurons to determine which types of behaviors they control, and finally c) measure the activity of Cre-expressing neurons in awake behaving mice to determine precisely when, during specific behavioral sequences, the Cre-expressing neurons are active. With these approaches, we are elucidating the neuronal “labeled lines” of communication that control hunger and compel eating.